The objective of this research is to elucidate the cellular events which occur during the differentiation of skeletal muscle and how nuclear-cytoplasmic interactions regulate the synthesis and assembly of gene products. The cellular events which occur during normal myogenesis will be characterized by utilizing the reversible suppression of myogenesis by carbon dioxide deficiency. The effect of introducing a heterotypic cell on the nuclear-cytoplasmic interactions which occur during normal muscle development will be studied by using skeletal:cardiac heterokaryons. My approach will be to correlate structural changes with cellular function by using the techniques of light and electron microscopy, autoradiography, gel electrophoresis and electrophysiology on muscle cells in culture. The long term objective of such studies is to provide basic information on the cellular events occuring during skeletal muscle development so that we may understand the factors regulating differentiation and the maintenance of normal structure and function. Such knowledge should prove beneficial to an understanding of muscle regeneration and repair in normal and diseased muscle.